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CW-270033, a novel pyrrolidinyl-thio carbapenem, has potent antimicrobial activity in vitro and in vivo.

Abstract
CW-270033, an injectable carbapenem, is a novel, synthesized pyrrolidinyl-thio carbapenem. In the present study, the in-vitro and in-vivo antibacterial activities of CW-270033 against wild-type strains and clinical isolates were compared with those of imipenem and meropenem. CW-270033 was more active than imipenem against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) clinical isolates, but was slightly less active than meropenem. Against the Gram-positive clinical isolates methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), CW-270033 was slightly more active than meropenem, but was less active than imipenem. CW-270033 displayed potent in-vivo activity against E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus SMITH in the mouse systemic infection model; the efficacy of CW-270033 in this model was 2--7 fold higher than that of meropenem. This activity was comparable to the in-vitro activity of CW-270033. An intravenous injection of CW-270033 showed that the half-life of CW-270033 in serum in mice was about 20 min, which was about two times that of meropenem. CW-270033 was also found to be resistant to hydrolysis by the mouse renal dehydropeptidase I (DHP-I) enzyme.
AuthorsJongMyeung Kim, Jong Ryul Ha, Se Woong Oh, Hong Gi Kim, Jin-Man Lee, Dong Gun Lee, Sang-Han Lee, Jong Guk Kim
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 30 Issue 3 Pg. 575-9 (Mar 2007) ISSN: 0918-6158 [Print] Japan
PMID17329859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • CW-270033
  • Carbapenems
  • Protease Inhibitors
  • Pyrrolidines
  • Thienamycins
  • Cilastatin
  • Meropenem
Topics
  • Animals
  • Anti-Bacterial Agents (administration & dosage, chemistry, pharmacology)
  • Bacteria (drug effects, growth & development)
  • Bacterial Infections (microbiology, prevention & control)
  • Carbapenems (administration & dosage, chemistry, pharmacology)
  • Cilastatin (administration & dosage, chemistry, pharmacology)
  • Dose-Response Relationship, Drug
  • Enterococcus faecalis (drug effects, growth & development)
  • Escherichia coli (drug effects, growth & development)
  • Injections, Intravenous
  • Meropenem
  • Methicillin Resistance
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Protease Inhibitors (administration & dosage, chemistry, pharmacology)
  • Pseudomonas aeruginosa (drug effects, growth & development)
  • Pyrrolidines (administration & dosage, chemistry, pharmacology)
  • Staphylococcus aureus (drug effects, growth & development)
  • Thienamycins (administration & dosage, pharmacology)
  • Vancomycin Resistance

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